EJHaem · 2026
Comparative Efficacy of Complement Inhibitors in Complement Inhibitor-Naïve PNH: A Systematic Review With Supportive Exploratory Network Meta-Analysis of Randomized Trials.
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Ishaque Rehan, Talpur Abdul Subhan, Sidra Hafiza, Memon Huda, Memon Furqan Tarique, Talat Fawad, Rafiq Taha, Rayamajhi Supratik
Аннотация
INTRODUCTION: Paroxysmal nocturnal haemoglobinuria (PNH) is an uncommon, life-threatening disease, caused by intravascular haemolysis by the complement system. In this review, we aim to compare the efficacy of the available agents across patient-centred outcomes in complement inhibitor-naive patients.
METHODS: Following PRISMA guidelines, a comprehensive literature search was conducted on PubMed, Cochrane CENTRAL and ClinicalTrials.gov for studies published up to 30th May 2025. A frequentist model network meta-analyses were conducted in RStudio (v5.4.1) using a common-effects model.
RESULTS: A total of four randomized controlled trials evaluating four complement inhibitor agents (ravulizumab, crovalimab, eculizumab and pegcetacoplan) were included in this systematic review and network meta-analysis, involving 589 complement inhibitor-naïve adults with PNH. Across outcomes, all active treatments demonstrated benefit compared with placebo or supportive care. In the exploratory network meta-analysis of transfusion avoidance, no consistent statistically significant differences were observed between active treatments, although ravulizumab showed higher odds compared with crovalimab (OR = 2.69, 95% CI: 1.13-6.41; p = 0.0256). For change in FACIT-Fatigue score, all active treatments improved fatigue versus placebo, with some statistically significant differences observed between agents; however, these comparisons were based on indirect evidence from a sparse network.
CONCLUSION: This study suggests that available complement inhibitors improve key outcomes versus placebo/supportive care in complement inhibitors naive PNH. However, the evidence network is sparse (four trials) and the cross-trial differences limit reliable inference regarding relative efficacy between active agents. Comparative findings should be interpreted as hypothesis-generating.
METHODS: Following PRISMA guidelines, a comprehensive literature search was conducted on PubMed, Cochrane CENTRAL and ClinicalTrials.gov for studies published up to 30th May 2025. A frequentist model network meta-analyses were conducted in RStudio (v5.4.1) using a common-effects model.
RESULTS: A total of four randomized controlled trials evaluating four complement inhibitor agents (ravulizumab, crovalimab, eculizumab and pegcetacoplan) were included in this systematic review and network meta-analysis, involving 589 complement inhibitor-naïve adults with PNH. Across outcomes, all active treatments demonstrated benefit compared with placebo or supportive care. In the exploratory network meta-analysis of transfusion avoidance, no consistent statistically significant differences were observed between active treatments, although ravulizumab showed higher odds compared with crovalimab (OR = 2.69, 95% CI: 1.13-6.41; p = 0.0256). For change in FACIT-Fatigue score, all active treatments improved fatigue versus placebo, with some statistically significant differences observed between agents; however, these comparisons were based on indirect evidence from a sparse network.
CONCLUSION: This study suggests that available complement inhibitors improve key outcomes versus placebo/supportive care in complement inhibitors naive PNH. However, the evidence network is sparse (four trials) and the cross-trial differences limit reliable inference regarding relative efficacy between active agents. Comparative findings should be interpreted as hypothesis-generating.